AUTHORS: Emily Sauck, DO, MBA and Anthony Sciscione, DO
Endometrial cancer, also called endometrial carcinoma (EC), is cancer of the endometrium, which is the lining of the uterus. Traditionally, EC was divided into two types: Type 1, which are estrogen-driven, and type 2, which are not estrogen driven. However, EC is now more commonly subdivided into different types based on histology-how the cells appear under the microscope (Table 1).
TABLE 1 Pathogenetic Subsets of Endometrial Carcinoma
Parameter | Type I | Type II |
---|---|---|
Age | 50s-60s | 60s-70s |
Obesity | Common | Uncommon |
Estrogenic stimuli | Common | Uncommon |
Endometrium | Anovulatory | Atrophic |
Precursor | Endometrial intraepithelial neoplasia | Presumed EmGD |
Transition | Slow | Unknown |
Type | Endometrioid | Papillary serous or mixed |
Molecular genetics | MSI, PTEN mutation; loss of PAX2 | p53 mutation, 1p deletions; loss of PAX2 |
Familial | Hereditary nonpolyposis colonic cancer syndrome | |
Spread | Lymph nodes | Peritoneum |
Concurrent ovarian | Common | Uncommon |
Prognosis | Good | Poor |
EmGD, Endometrial glandular dysplasia; MSI, microsatellite instability.
From Crum CP et al: Diagnostic gynecologic and obstetric pathology, ed 3, Philadelphia, 2018, Elsevier.
Histologic types are summarized in Box 1 and include adenocarcinoma, uterine carcinosarcoma, squamous cell carcinoma, small cell carcinoma, transitional carcinoma, and serous carcinoma, with most endometrial cancers being adenocarcinomas and endometrioid cancer being the most common type of adenocarcinoma.
BOX 1 Endometrial Primary Adenocarcinomas
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From Gershenson DM et al: Comprehensive gynecology, ed 8, Philadelphia, 2022, Elsevier.
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Age: Most cases are diagnosed in postmenopausal women, with a median age of 63 yr.
Estrogen exposure/hormone imbalance: Whether from early menarche, late menopause, diabetes, nulliparity, tamoxifen use, polycystic ovary syndrome, or unopposed estrogen therapy, the more exposure the endometrium has to estrogen, the more a womans risk of developing EC increases.
TABLE 2 Risk Factors for Endometrial Cancer
Factor | Relative Risk | ||
---|---|---|---|
Overweight (lbs): | |||
3.0 | |||
10.0 | |||
Nulliparous: | |||
2.0 | |||
5.0 | |||
Late menopause (>52 vs. 49 yr) | 2.4 | ||
Diabetes mellitus | 2.7 | ||
Unopposed estrogen therapy | 6.0 | ||
Tamoxifen therapy | 2.0 | ||
Sequential oral contraceptives | 7.0 | ||
Combination oral contraceptives | 0.5 | ||
Cowden syndrome (PTEN mutation) | Three- to fivefold increased risk | ||
Hereditary nonpolyposis colonic cancer syndrome | 40%-60% lifetime risk | ||
Family member with endometrial cancer | 3.4 |
From Crum CP et al: Diagnostic gynecologic and obstetric pathology, ed 3, Philadelphia, 2018, Elsevier.
∗Previously termed adenoacanthoma or adenosquamous carcinoma.
TABLE 4 National Comprehensive Cancer Network Treatment Guidelines for Endometrial Carcinoma After Comprehensive Surgical Staging
Stage IA | |||
Grade 1 without ARF | Observe | ||
Grade 1 with ARF | Observe or VBT | ||
Grade 2 or 3 without ARF | Observe or VBT | ||
Grade 2 or 3 with ARF | Observe or VBT and/or pelvic RT | ||
Stage IB | |||
Grade 1 without ARF | Observe | ||
Grade 1 with ARF | Observe or VBT | ||
Grade 2 without ARF | Observe or VBT | ||
Grade 2 with ARF | Observe or VBT and/or pelvic RT | ||
Grade 3 without ARF | Observe or VBT and/or pelvic RT | ||
Grade 3 with ARF | Observe or VBT and/or pelvic RT ± chemotherapy | ||
Stage II | |||
Grade 1 | VBT and/or pelvic RT | ||
Grade 2 | Pelvic RT and VBT | ||
Grade 3 | Pelvic RT and VBT ± chemotherapy | ||
Stage IIIA | Chemotherapy ± pelvic RT or tumor-directed RT ± chemotherapy or pelvic RT ± VBT | ||
Stage IIIB-IIIC | Chemotherapy and/or tumor-directed RT | ||
Stage IVA-IVB | Chemotherapy ± RT |
ARF, Adverse risk factors (age, positive lymphovascular space invasion, tumor size, lower uterine or cervical involvement); RT, radiation therapy; VBT, vaginal brachytherapy.
From Niederhuber JE: Abeloffs clinical oncology, ed 6, Philadelphia, 2020, Elsevier.
TABLE 5 Revised FIGO Staging for Endometrial Cancer (adopted 2009)
Stages∗ | Characteristic | ||
---|---|---|---|
I | Tumor confined to the corpus uteri | ||
IA | No or less than half myometrial invasion | ||
IB | Invasion equal to or more than half of the myometrium | ||
II | Tumor invades cervical stroma but does not extend beyond the uterus | ||
III | Local or regional spread of the tumor | ||
IIIA | Tumor invades serosa of the corpus uteri or the adnexa | ||
IIIB | Vaginal or parametrial involvement | ||
IIIC | Metastases to pelvic or paraaortic lymph nodes | ||
IIIC1 | Positive pelvic nodes | ||
IIIC2 | Positive paraaortic lymph nodes with or without positive pelvic lymph nodes | ||
IV | Tumor invades bladder or bowel mucosa, or distant metastasis | ||
IVA∗ | Tumor invasion of bladder or bowel mucosa | ||
IVB | Distant metastases, including intraabdominal or inguinal lymph nodes |
FIGO, Fédération Internationale de Gynécologie et dObstétrique (International Federation of Gynecology and Obstetrics).
Endocervical glandular involvement should be considered only as stage I and no longer as stage II.
Positive cytology has to be reported separately without changing the stage.
From Lobo RA et al: Comprehensive gynecology, ed 7, Philadelphia, 2017, Elsevier.
TABLE 3 Differential Diagnosis of Endometrial Carcinoma (Curettings)
Parameter | Mimicking | Differential Diagnosis |
---|---|---|
Gland architecture | Cancer | Telescoping artifact; stromal collapse breakdown; sectioning artifacts |
Benign | Microglandular mucinous carcinoma; surface endometrioid carcinoma | |
Nuclear atypia | Cancer | Surface or glandular repair; Arias-Stella changes (hormonal therapy); radiation effect |
Papillary changes | Cancer | Exfoliation artifact; stromal breakdown with papillary changes; papillary syncytial changes |
Benign | Papillary mucinous carcinoma |
From Crum CP et al: Diagnostic gynecologic and obstetric pathology, ed 3, Philadelphia, 2018, Elsevier.
Figure E2 A 48-yr-old woman with endometrial carcinoma.
A, Endovaginal ultrasound (US) showing thickened, heterogeneous, cystic, and vascular hyperechoic tissue filling the endometrial cavity (arrows). B, Second sagittal US image showing the same (arrows).
From Fielding JR et al: Gynecologic imaging, Philadelphia, 2011, Saunders.
Figure E3 A 56-yr-old woman with endometrial carcinoma.
A, Sagittal ultrasound (US) image showing thickened cystic echogenic soft tissue filling the endometrial cavity (arrows). B, Axial US image showing thickened cystic echogenic soft tissue filling the endometrial cavity (arrows). C, Noncontrast-enhanced axial computed tomographic (CT) image showing low-attenuation tissue filling the endometrial canal (arrows) in a postmenopausal patient. Note fundal thinning. D, Noncontrast-enhanced axial CT image showing cervical soft tissue fullness.
From Fielding JR et al: Gynecologic imaging, Philadelphia, 2011, Saunders.
Any woman with postmenopausal bleeding or abnormal uterine bleeding with risk factors for endometrial cancer needs evaluation by a gynecologist and either endometrial biopsy and/or pelvic ultrasound. When endometrial cancer is diagnosed, the patient should be cared for by a gynecologic oncologist and undergo surgical staging in a minimally invasive procedure when possible.
Endometrial Cancer (Patient Information)
Abnormal Uterine Bleeding (Related Key Topic)
Uterine Malignancy (Related Key Topic)